Antitumor activity of 7-n-(p-hydroxyphenyl)-mitomycin C in experimental tumor systems.
The antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) was compared with that of mitomycin C (MMC) in rodent tumor systems. M-83 exhibited more potent activity than MMC against the ascitic form of lymphocytic leukemia P388 and fibrosarcoma Meth 1, and doses of over 5 mg/kg of M-83 (1/6 LD50) resulted in some 60-day survivors. The chemotherapeutic ratio (optimal dose/MED) of M-83 was around 64 and was estimated to be approximately 5 to 8 times higher than that of MMC. Upon intravenous administration, M-83 also gave a better survival and showed a higher chemotherapeutic ratio than MMC against intravenously implanted P388. M-83 inhibited the growth of solid form of sarcoma 180 to the same extent as MMC at an equivalent dose, but showed a higher safety margin than MMC. M-83 was as effective as MMC against Lewis lung carcinoma at dose levels giving the same degree of toxicity. In vitro studies on tumor growth inhibition demonstrated that the cytotoxic effects of M-83 against leukemia P388 and fibrosarcoma Meth 1 cells were similar to and stronger than those of MMC, respectively.
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005354:Fibrosarcoma / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012510:Sarcoma 180 / Q000188:drug therapy
D008937:Mitomycins; D016685:Mitomycin; C027281:7-N-(4-hydroxyphenyl)mitomycin C